Avanafil (AVN) is a new selective phosphodiesterase-5 (PDE-5) inhibitor, which is used as an oral treatment of
erectile dysfunction. Coadministration of avanafil (AVN) with some antihypertensive drugs especially in elderly
patients is a very common case. Nimodipine (NIM) is one of these hypotensive drugs that are commonly
coadministered. Synergistic hypotension effect as a result of AVN and NIM coadministration is expected;
therefore, it is mandatory to study the possible pharmacokinetic interaction between them. The main aim of the
current work is to develop a simple, sensitive, and selective electrochemical method for simultaneous determination of AVN and NIM in human serum samples. Nickel oxide nanoparticles/poly(sulfanilamide) film was
used as a new electrochemical modifier, which is electrodeposited on the surface of pencil graphite electrode
(PGE) to improve its electrochemical properties. The best resolution between the two studied drugs was achieved
by using Britton-Robinson buffer (BRB) at pH 3.0 producing two peaks at 1.45 V and 0.80 V for AVN and NIM,
respectively. Furthermore, cyclic voltammetry was utilized for the first time to study the oxidation behavior of
AVN and NIM and a plausible oxidation mechanism was suggested for both of them. The proposed square wave
voltammetric method was successfully applied for trace quantification of AVN and NIM in real human serum
samples with detection and quantitation limits of 0.037 and 0.10 μmol L- 1 for AVN and 0.32 and 0.98 μmol L- 1
for NIM, respectively. Moreover, the suggested approach was effectively implemented to investigate the possible
pharmacokinetic interaction between AVN and NIM in serum samples of heathy human male volunteers. It was
found from the pharmacokinetic parameters calculated for AVN when administered alone or in presence of NIM
that there is a significant increase of serum concentration of AVN, when it is coadminstered with NIM, which
stresses the importance of dose adjustment of AVN when coadministered with NIM.